An Exploratory Clinical Study of Anti-CD19 CAR NK Cells in the Treatment of Systemic Lupus Erythematosus

NCT06010472 | Recruiting Early Phase 1 DMC

• 1 other identifier: CHEC2023-174
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-cluster of differentiation antigen 19 (CD19) chimeric antigen receptor (CAR) natural killer (NK) cells (KN5501) in patients with moderate to severe refractory systemic lupus erythematosus (SLE). 36 patients are planned to be enrolled in the dose-escalation trial. The primary objective of the study was to evaluate the safety of allogeneic anti-CD19 CAR-NK cells (KN5501) for the treatment of patients with moderate to severe refractory active SLE. The secondary objective is to evaluate the efficacy of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe refractory SLE, including British Isles Lupus Assessment Group 2004 (BILAG-2004) index, Systemic Lupus Erythematosus Responder Index (SRI)-4 response rate, Lupus Low Disease Activity State (LLDAS) rate, and Definitions Of Remission In SLE (DORIS) remission rate.

Conditions

Systemic Lupus Erythematosus (SLE)

Keywords

Lupus Erythematosus, Systemic; Autoimmune disorders; Connective Tissue Diseases

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose Limiting Toxicity (DLTs)

  To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE

  within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE

  within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion

Secondary Outcomes (3)

• SRI-4 response rate of subjects

  12, 24,36, and 52 weeks after infusion

• LLDAS rate of subjects

  12, 24,36, and 52 weeks after infusion

• DORIS remission rate of subjects

  12, 24,36, and 52 weeks after infusion

Study Arms (1)

anti-CD19 CAR NK cells

EXPERIMENTAL

To evaluate the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe refractory SLE. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19 CAR NK cells infusion.

Drug: anti-CD19 CAR NK cells (KN5501)

Interventions

anti-CD19 CAR NK cells (KN5501) DRUG

Patients will receive Fludarabine (25 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Multiple doses of anti-CD19 CAR NK cells (KN5501) will infused in each group using the "3 + 3" dose-escalation strategy.

anti-CD19 CAR NK cells

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥ 18 years old and ≤ 65 years old, male or female, subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF)
• Previous diagnosis of systemic lupus erythematosus (SLE) (according to the 1997 American Rheumatology Association criteria)
• Females of childbearing potential must use effective contraception during study treatment and for 90 days after the last dose of study treatment. In addition, subjects must not donate eggs during the study and for at least 90 days after the last dose of study treatment
• Subjects with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score ≥ 8 points prior to screening
• Subject has ≥ 1 organ system with BILAG-2004 Class A mobility score or ≥ 2 organ systems with BILAG-2004 Class B mobility score prior to screening
• Subjects meets one of the following:
• Antinuclear antibody (ANA) ≥ 1:80, determined by immunofluorescence method;
• Anti-dsDNA antibodies are higher than normal level;
• Anti-Smith antibodies are higher than normal level
• Absolute number of neutrophils ≥ 1.0×10\^9/L, hemoglobin ≥ 60g/L
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Subjects have been treated with oral corticosteroids (OCS) in combination with an immunosuppressive or biologic agent for at least 6 months prior to enrollment

You may not qualify if:

• Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), or subjects with a history of severe allergic reactions
• Subjects with active infection receiving intravenous (IV) antibiotic treatment, or received intravenous (IV) antibiotic treatment within one week prior to anti-CD19 CAR NK Cells infusion
• Subjects with acquired and congenital immunodeficiency diseases
• Subjects with grade III or IV heart failure (NYHA classification)
• History of epilepsy or other central nervous system (CNS) diseases
• History of severe herpetic infection, such as herpetic encephalitis, ocular herpes, or diffuse herpes
• History of other primary malignant tumors except:
• Cured non-melanoma skin cancer by surgical excision, for example basal cell carcinoma (BCC) ;
• Cured primary malignant tumors, such as cervical cancer, superficial bladder cancer, breast cancer
• Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening; History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of anti-CD19 CAR NK Cells (KN5501), except for lupus (determined by the investigator)
• Females who are pregnant, lactating, or planning a pregnancy within six months
• Any active skin disease that may interfere with the study assessment of SLE, including but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE cutaneous lupus manifestations (eg, cutaneous vascular disease, periungual telangiectasia, fingertip sclerosis, rheumatoid nodules, erythema multiforme, leg ulcers) or drug-induced lupus
• Subjects who have received other clinical trial treatment within 3 months
• Subjects who have received B cell-targeted drug therapy within 1 month before enrollment
• Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome

Sponsors & Collaborators

• Changhai Hospital: lead
• Rui Therapeutics Co., Ltd: collaborator

Study Sites (1)

Changhai Hospital

Shanghai, China

RECRUITING

Related Publications (1)

• Gao J, Li M, Sun M, Yu Y, Kong R, Xu X, Liu S, Chen Q, Li X, Wu Y, Xu E, Yang J, Zhao D. Efficacy and safety of allogeneic CD19 CAR NK-cell therapy in systemic lupus erythematosus: a case series in China. Lancet. 2026 Dec 20;406(10522):2968-2979. doi: 10.1016/S0140-6736(25)01671-X. Epub 2025 Nov 12.

  PMID: 41240964 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Autoimmune Diseases; Connective Tissue Diseases

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases; Immune System Diseases

Study Officials

• Dongbao Zhao, Doctor

  ChanghaiHospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dongbao Zhao, Doctor

CONTACT

+86-15921061314; dongbaozhao@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: August 24, 2023
• Study Start: August 20, 2023
• Primary Completion (Estimated): August 25, 2026
• Study Completion (Estimated): August 25, 2027
• Last Updated: April 29, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)